We have been studying the structure and function of Cro repressor of bacteriophage lambda in a hope to understand gene regulation at a molecular level. Since we know the 3-D structure of Cro repressor, we are now at a position to study interaction of this repressor with operator DNA at a real molecular level. Out approach includes chemical synthesis of wild type and mutant operator DNAs to find out the essential group;s in this interaction. Two lines of experiments are planned. In one experiment, a series of operator DNAs which have a base substitution will be chemically synthesized, cloned onto a phage lambdai21 or a plasmid pBR322, and assayed for Cro binding ability. Then, some of these operators DNAs willbe used for co-crystalization with Cro repressor, which will be analyzed by X-ray crystallographers. Through these experiments, we wish to build a molecular model for Cro repressor-operator interaction.